Time-of-flight mass spectrometry (TOFMS) is based upon the principle that ions of different mass to charge ratios travel at different velocities such that a packet of ions accelerated to a specific kinetic energy separates out over a defined distance according to the mass to charge ratio. By detecting the time of arrival of ions at the end of the defined distance, a mass spectrum can be built up.
Orthogonal TOFMSs operate in so-called cyclic mode, in which successive packets of ions are accelerated to a kinetic energy, separated in flight according to their mass to charge ratios, and then detected. The complete time spectrum in each cycle is detected and the results added to a histogram.
It has been observed that ions of a particular mass to charge ratio typically reach the detector with a range of arrival times. The range of arrival times can be due to effects of location in the extraction field at the output of the ion source, and the initial kinetic energy, which ultimately results in reduced resolution.
To maintain high mass accuracy in a TOFMS, high stability of the calibration of the mass spectrometer must be maintained. This means that the flight time for ions of substantially the same mass must be substantially constant over time. The flight time for ions of substantially the same mass can be influenced by temperature. The materials from which the optical elements of the instrument are constructed will undergo thermal expansion or thermal contraction as the temperature varies. Thermal expansion or contraction can affect both the lengths and electric field gradients which in turn affect the flight times of ions through the mass spectrometer.
The calibration function of a TOFMS is approximately a linear relationship between the ion mass and the square of the ion flight time. For accurate results the calibration may be slightly non-linear to account for subtle differences in initial starting positions and energies (hence resulting in a calibration curve). The two main factors that affect the stability of the calibration curve, and hence the constancy of flight times, are firstly the drift in the voltages applied to the ion-optical elements and secondly the thermal expansion or contraction effect within the construction materials of the elements defining the flight path of the ions.
Drift in voltage supplies that are applied to the ion-optical elements are largely due to thermal effects, and to minimize this, the voltage providing power supplies can be housed in a thermally stabilized environment.
Providing compensation for the thermal drift (thermal expansion or contraction) of the construction materials of the elements defining the flight path of the ions is a focus of the invention.
One method of dealing with the thermal drift described above is to use internal standards. An internal standard is a compound of known mass which is analyzed together with the sample under analysis. The deviation of the measured mass of the internal standard to the known mass of the internal standard can be employed to correct the calibration curve and restore the correct value for the standard. In order to best account for non-linear affects of internal standard, the internal standard is added to the sample under analysis, so that it is subjected to the same ionisation and instrumental conditions. The disadvantage of this is that there may be interference of the standard in the mass spectrum when unknown samples are being analyzed, and there is competition for ionization with the sample molecules, unless ionized in a separate source. When obtaining a mass spectrum over a broad range of masses, it is beneficial to use internal standards that are close in mass to the masses of interest to account for non-linearity in the calibration curve.
Another method of dealing with the thermal drift of the construction materials is to compensate for the thermal expansion effects. The temperature of the elements in the flight path can be measured, for example with thermocouples, and a correction made to the calibration curve based on the changes measured. These methods typically require very accurate measurement of the temperature, and that adds additional costs and complexity in the control system and software required.
Yet another method of dealing with the thermal drift of the construction materials is to control the spacing between the ion elements and the optical elements via an external control mechanism such that the flight time does not vary with temperature. Once again, this adds additional costs and complexity to the instrument.
Another solution is to control the spacing between the ion elements and the optical elements via internal control mechanisms (such an inherent properties of the construction materials) such that the flight time does not vary with temperature. One can use construction materials with negligible thermal expansion coefficients. However it is not currently practical to build an entire structure out of such materials. A compromise is to build combinations of construction material with different thermal expansion coefficients, such that the effects of their thermal expansions compensate for each other, and the lengths of the various ion and/or optical elements remain constant, but this can mean complex construction.
A further method of dealing with the thermal drift of the construction materials is to enclose the entire instrument in a temperature controlled environment to maintain an accurate constant temperature. Since most TOFMSs are relatively large instruments, implementation of this method adds considerably cost to the instrument.
There is a need for a solution to thermal compensation for elements of a TOFMS such that the desired level of mass accuracy can be achieved.